The following includes information that may be useful in understanding the present invention. It is not an admission that any of the information, publications or documents specifically or implicitly referenced herein is prior art, or essential, to the presently described or claimed inventions. All publications and patents mentioned herein are hereby incorporated herein by reference in their entirety.
Portable infusion devices and systems have been used for dispensing compositions in the care of patients with diseases, disorders and conditions that may be treated with insulin. These devices and systems are used to dispense insulin in a controlled setting. Insulin infusion pumps are used by many people with diabetes.
Diabetes is caused by a deficiency of beta-cell hormone secretion. Sixty-five years after the discovery of insulin, a second beta-cell hormone, amylin, was discovered. Amylin is a peptide hormone that is released into the bloodstream by the β-cells of the pancreas along with insulin, after a meal. Nearly 60 different effects have been reported in various experiments using amylin (or the amylin agonist analog, pramlintide) in a variety of species. In glucose metabolism amylin's main actions conspire to control the rate of nutrient entry into plasma, in contrast with actions of insulin to accelerate nutrient disposal (e.g., into muscle and other insulin-sensitive tissues).
Given that evolution selected for two beta-cell hormones to control glucose metabolism, it has been proposed that dual hormone replacement would be optimal therapy for patients with diabetes, especially in the case of type 1 diabetes (T1D) where beta-cell function is completely gone and, like insulin, amylin is absent. See U.S. Pat. Nos. 5,124,314 and 6,136,784. Benefits reported by some patients who have used amylin replacement therapy with the compound pramlintide per its package insert instructions in addition to their insulin therapy support this hypothesis. In some of those patients, the benefits included lower HbA1c and less variability in plasma glucose levels and/or weight loss.
Pramlintide (25,28,29Pro-h-amylin) is an agonist of amylin. Like amylin, it has been reported to aid in the absorption of glucose by slowing gastric emptying, promoting satiety, and inhibiting secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin. E.g., Huffman D M, McLean G W, Seagrove M A (2009). “Continuous Subcutaneous Pramlintide Infusion Therapy in Patients with Type 1 Diabetes: Observations from a Pilot Study” Endocrine Practice 15(7): 689-695. Pramlintide has been approved by the FDA for use by T1D and type 2 diabetics (T2D) who use insulin. E.g., Ryan G J, Jobe L J, Martin R (2005). “Pramlintide in the treatment of type 1 and type 2 diabetes mellitus” Clinical Therapeutics 27(10): 1500-1512. Pramlintide is said to allow patients to use less insulin, to lower average blood sugar levels, and to substantially reduce what otherwise would be a large unhealthy rise in blood sugar that occurs in diabetics right after eating. Apart from insulin analogs, pramlintide is the only drug approved by the FDA to lower blood sugar in T1D since insulin in the early 1920s.
Given the number of people who need insulin, if a significant percentage of patients on insulin replacement therapy upgraded to dual hormone replacement therapy, pramlintide would be a major drug in the diabetes category. However, since its market launch pramlintide has never risen above a niche product. Two problems may have discouraged patients and caregivers. The first is multiple injections. Many patients who respond well to the drug can grow tired of pre-meal injections, and many patients who may benefit from pramlintide are put off by the idea of three more daily shots.
The second is adverse events. During the time it has been on the market, a perception has developed that pramlintide has a low therapeutic index; it does not deliver strong enough benefits to offset its downsides, particularly nausea and hypoglycemia if insulin dosing is not properly adjusted to reflect co-administration with pramlintide. Initial startup nausea is often mentioned as a concern among patients considering trial of pramlintide.
A method for the treatment of diabetes mellitus in a mammal comprising the administration of a therapeutically effective amount of pramlintide and a therapeutically effective amount of an insulin was patented nearly 20 years ago, in 1997 (U.S. Pat. No. 5,686,411 for “Amylin agonist peptides and uses therefor”). However, no such product or combination therapy was ever developed or marketed.
There remains a need in the art for new devices, methods, and therapeutics useful in treating patients having diseases, disorders, and conditions that are treated with insulin and/or amylin, or their analogues, including T1D and T2D. There is a particular need for new devices and therapeutics that span the entire spectrum of diseases, disorders, and conditions associated with amylin deficiency, particularly those that are also benefited by treatment with insulin. Such devices, methods, and therapeutics are described and claimed herein.